Research into the pharmacology of glucocorticoids on motor nerve excitability will continue. Studies by this group have partly defined: (a) the nature of an ultimate and striking glucocorticoid induced neuronal increase in excitability; (b) located the distal axon and terminals as the region of motor nerve affected; (c) ruled out perikaryal involvement; (d) described the molecular requirements associated with this glucocorticoid effect and (e) uncovered the evolution of this glucocorticoid action on neurons, wherein an initial, transient selective suppressaon of a facilitatory function of motor nerve terminals is superceded by an increased facilitatory function. Projected work will aim to define: (a) distal axonal memebranes as the site of action; (b) the membrane labilizing action; (c) effect on presynaptic transmitter dynamics; (d) the pharmacokinetic parameters of this glucocorticoid effect, including the relationship between blood levels, motor nerve uptake, motor nerve concentration and its regional distribution, rate of neuronal loss and influence of the metabolic susceptibility of the glucococorticoid. Physiologic, as well as therapeutic significances will be south via parallel studies with adrenalectomized animals. Our work has also established that intensive glucocorticoid treatment will preserve motor nerve terminal excitability and transmission during early Wallerian degeneration. The studies projected above will be pursued with our in vivo model of subacute motor neuron degeneration in order to give further insight into glucocorticoid interaction with degenerating membranes. Similar work will be initiated to study effects on segmental denervation in spinal cord pathways. BIBLIOGRAPHIC REFERENCES: W.F. Riker, T. Baker and M. Okamoto. Glucocorticoids and mammalian motor nerve excitability. Arch. Neurol. 32:688-694, 1975. T. Baker, W.F. Riker and E. Hall. Further studies on @lucorcorticoid effects on motor nerve endin excitability. Neuroscience Abstracts 2 (in press) 1976.